Department of Pediatrics, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Center for Artificial Intelligence in Medicine and Imaging, Stanford University, Stanford, CA, USA.
J Cachexia Sarcopenia Muscle. 2021 Aug;12(4):1024-1033. doi: 10.1002/jcsm.12734. Epub 2021 Jun 29.
Survival from paediatric high-risk neuroblastoma (HR-NBL) has increased, but cis-retinoic acid (cis-RA), the cornerstone of HR-NBL therapy, can cause osteoporosis and premature physeal closure and is a potential threat to skeletal structure in HR-NBL survivors. Sarcopenia is associated with increased morbidity in survivors of paediatric malignancies. Low muscle mass may be associated with poor prognosis in HR-NBL patients but has not been studied in these survivors. The study objective was to assess bone density, body composition and muscle strength in HR-NBL survivors compared with controls.
This prospective cross-sectional study assessed areal bone mineral density (aBMD) of the whole body, lumbar spine, total hip, femoral neck, distal 1/3 and ultradistal radius and body composition (muscle and fat mass) using dual-energy X-ray absorptiometry (DXA) and lower leg muscle strength using a dynamometer. Measures expressed as sex-specific standard deviation scores (Z-scores) included aBMD (adjusted for height Z-score), bone mineral apparent density (BMAD), leg lean mass (adjusted for leg length), whole-body fat mass index (FMI) and ankle dorsiflexion peak torque adjusted for leg length (strength-Z). Muscle-specific force was assessed as strength relative to leg lean mass. Outcomes were compared between HR-NBL survivors and controls using Student's t-test or Mann-Whitney U test. Linear regression models examined correlations between DXA and dynamometer outcomes.
We enrolled 20 survivors of HR-NBL treated with cis-RA [13 male; mean age: 12.4 ± 1.6 years; median (range) age at therapy initiation: 2.6 (0.3-9.1) years] and 20 age-, sex- and race-matched controls. Height-Z was significantly lower in HR-NBL survivors compared with controls (-1.73 ± 1.38 vs. 0.34 ± 1.12, P < 0.001). Areal BMD-Z, BMAD-Z, FMI-Z, visceral adipose tissue and subcutaneous adipose tissue were not significantly different in HR-NBL survivors compared with controls. Compared with controls, HR-NBL survivors had lower leg lean mass-Z (-1.46 ± 1.35 vs. - 0.17 ± 0.84, P < 0.001) and strength-Z (-1.13 ± 0.86 vs. - 0.15 ± 0.71, P < 0.001). Muscle-specific force was lower in HR-NBL survivors compared with controls (P < 0.05).
Bone mineral density and adiposity are not severely impacted in HR-NBL survivors with growth failure, but significant sarcopenia persists years after treatment. Future studies are needed to determine if sarcopenia improves with muscle-specific interventions in this population of cancer survivors.
儿科高危神经母细胞瘤（HR-NBL）患者的生存率有所提高，但作为 HR-NBL 治疗基石的顺式维甲酸（cis-RA）可导致骨质疏松症和过早的骺板闭合，对 HR-NBL 幸存者的骨骼结构构成潜在威胁。肌肉减少症与儿科恶性肿瘤幸存者的发病率增加有关。肌肉量低可能与 HR-NBL 患者的预后不良有关，但尚未在这些幸存者中进行研究。本研究旨在评估 HR-NBL 幸存者与对照组之间的骨密度、身体成分和肌肉力量。
这项前瞻性的病例对照研究使用双能 X 射线吸收法（DXA）评估了全身、腰椎、全髋、股骨颈、远端 1/3 和超远端桡骨的骨矿物质密度（aBMD），并使用测力计评估了下肢肌肉力量。用身高 Z 分数（aBMD）、骨矿物质表观密度（BMAD）、下肢瘦体重（下肢长度调整）、全身脂肪质量指数（FMI）和下肢长度调整的踝背屈峰值扭矩（强度 Z）表示的身体成分（肌肉和脂肪质量）表示为性别特异性标准偏差分数（Z 分数）。肌肉特异性力被评估为与下肢瘦体重的比值。使用学生 t 检验或曼-惠特尼 U 检验比较 HR-NBL 幸存者和对照组之间的结果。线性回归模型检查了 DXA 和测力计结果之间的相关性。
我们纳入了 20 名接受 cis-RA 治疗的 HR-NBL 幸存者（13 名男性；平均年龄：12.4 ± 1.6 岁；中位（范围）治疗开始年龄：2.6（0.3-9.1）岁）和 20 名年龄、性别和种族匹配的对照组。HR-NBL 幸存者的身高 Z 分数明显低于对照组（-1.73 ± 1.38 比 0.34 ± 1.12，P < 0.001）。与对照组相比，HR-NBL 幸存者的全身 aBMD-Z、BMAD-Z、FMI-Z、内脏脂肪组织和皮下脂肪组织无显著差异。与对照组相比，HR-NBL 幸存者的下肢瘦体重 Z 分数（-1.46 ± 1.35 比 -0.17 ± 0.84，P < 0.001）和强度 Z 分数（-1.13 ± 0.86 比 -0.15 ± 0.71，P < 0.001）较低。与对照组相比，HR-NBL 幸存者的肌肉特异性力较低（P < 0.05）。
在生长发育不良的 HR-NBL 幸存者中，骨矿物质密度和肥胖症没有受到严重影响，但在治疗多年后仍存在明显的肌肉减少症。需要进一步的研究来确定肌肉特异性干预措施是否可以改善该人群中癌症幸存者的肌肉减少症。
